A better understanding of metabolic disorders which affect the nervous system is the goal of this project. In some phases, the studies are purely diagnostic and area applied to assist in identifying the less common disorders of metabolism. Other phases deal with biochemical observations in known disorders that suggest steps in the pathogenesis of the disease. In some poorly understood groups of neurologic disease, studies are conducted to draw biochemical correlations where none had previously been known or were poorly developed. Therapeutic trials are conducted in selected disorders. A new phenotype of glycerol kinase deficiency has been identified. Pyruvate dehydrogenase complex has been examined in subjects with spinocerebellar degenerations. Contrary to published reports, no deficiency of this enzyme has been established in any case. Work has begun to examine other oxidative enzymes in these diseases. In addition, hexosaminidase has been measured in these patients and found to be normal in all cases. Neurotransmitter alterations have been suggested by the clinical status of this group and study of their neurotransmitter concentrations and metabolites has begun.